Reuben Kapur, Ph.D.
Frieda & Albrecht Kip Endowed Professor of Pediatrics; Director, Program in Hematologic Malignancies & Stem Cell Biology; Professor of Molecular Biology & Biochemistry, Medical & Molecular Genetics, Microbiology & Immunology
Description and summary of research focus of the laboratory
In adults, bone marrow (BM) is the major site for the continuous production of mature blood cells. Mature blood cells arise from hematopoietic stem cells (HSC) within the bone marrow cavity. While the regulation of HSCs is an extremely popular area of investigation; how this occurs remains an enigma. It is thought that part of this process involves self-renewal, differentiation and apoptosis or senescence. Although the precise mechanism(s) by which these fates are determined is still unclear, several molecules have been implicated in these processes, including components of the BM microenvironment. The BM microenvironment consists of extracellular matrix proteins as well as cells such as osteoblasts and stromal cells which contribute to hematopoietic stem/progenitor (HSC/P) cell fate by anchoring these cells in the BM cavity and delivering adhesive signals as well as signals in the form of soluble ligands, including cytokines and chemokines. These signals induce intracellular activation of both the positive regulators of HSC/P cell growth, self-renewal and differentiation as well as negative signals. Some of these pathways, such as those initiated by stem cell factor (SCF), the ligand for KIT, stromal cell derived factor-1 (SDF-1), and thrombopoietin (TPO), induce the activation of phosphatidylinositol 3’ kinase (PI3K), Src kinase (SFK) and focal adhesion kinase (FAK). How PI3K and its downstream targets including members of Rho family GTPases contribute to HSC/P regulation and the regulation of myeloid lineage derived macrophages, mast cells as well as neutrophils are a major area of ongoing research in Kapur lab.
Myeloproliferative disorder (MPD) is a heterogeneous group of hematologic malignancies which share the common characteristics of myeloid cell overproduction. The clinical diagnosis is designated on the principal cell lineage that is over-produced; however, commonly multiple myeloid components are increased. With the exception of chronic myelogenous leukemia (CML), therapeutic intervention for these diseases is largely ineffective. An additional major goal of Kapur lab is to elucidate the aberrant signaling mechanism(s) induced by activating BCR-ABL, FLT3, and KIT mutations that promote pathologic overproduction of myeloid cells in CML, AML and in systemic mastocytosis (SM), respectively, with the intent of defining novel therapeutic targets in these diseases. Kapur lab is using pharmacologic, genetic and biochemical approaches including established as well as newly created mouse models of leukemogenesis that recapitulate the human disease to accomplish these goals.
- Vemula S, ramdas G, Hanneman P, Martin J, Beggs HE, and Kapur R. Essential role for focal adhesion kinase in regulating stress hematopoiesis. Blood. Nov 18;116(20):4103-15, 2010. PMCID: PMC2993618
- Wu X, Chen S, Orlando SA, Yuan J, Kim ET, Munugalavadla V, Mali RS, Kapur R, and Yang FC. p85alpha regulates osteoblast differentiation by cross-talking with the MAPK pathway. J Biol Chem. Apr 15;286(15):13512-21, 2011. PMCID: PMC3075697
- Ma P, Mali RS, Munugalavadla V, Krishnan S, Ramdas B, Sims E, Martin H, Ghosh J, Li S, Chan RJ, Krystal G, Craig AW, Takemoto C, and Kapur R. The phosphatidylinositol-3-kinase pathway via microphthaimia transcription factor dirves the maturation of mast cells. Blood. Jul 15, 2011 (Epub ahead of print).
- Ma P, Vemula S, Munugalavadla V, Chen JB, Sims E, Borneo J, Kondo T, Ramsas B, Mali RS, Li S, Hashino E, Takemoto C, and Kapur R. Balanced Interactions between Lyn, p85α regulatory Subunit of Class IA Phosphatidylinositol-3-kinase and SHIP is Essential for Mast Cell Growth and Maturation. Molecular and Cellular Biology. Jul 2011. In press.
- Mali R, Ramdas B, Ma P, Shi J, Munugalavadla V, Sims E, Wei L, Vemula S, Nabinger SC, Goodwin CB, Chan RJ, Traina F, Visconte V, Tiu RV, Lewis TA, Stern AM, Wen Q, Crispino JD, Boswell HS and Kapur R. Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3 and BCR-ABL. Cancer Cell. Jul 2011. In press.
- B.S., 1985, Christ Church College, Kanpur, India
- B.S., 1989, Washington State University, Pullman, WA
- Ph.D., 1994, University of Arizona, Tucson, AZ